Study the Effect of Avanafil on the Pharmacodynamics and Pharmacokinetics of Warfarin in Healthy Male Subjects
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Phase I, Single-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel-Arm Study of the Effects of Avanafil on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Male Subjects|
- Pharmacokinetics - PK parameters AUC, C-max and t-max of R-and S-warfarin [ Time Frame: 24 hrs ] [ Designated as safety issue: Yes ]
- Pharmacodynamics - Prothrombin time, INR values, and area under effect-time curve (AUEC) of prothrombin and INR on days 14 and 15 [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
|Study Start Date:||April 2010|
|Study Completion Date:||May 2010|
|Primary Completion Date:||May 2010 (Final data collection date for primary outcome measure)|
Drug: 200 mg Avanafil
2 X 100mg tablets avanafil
|Placebo Comparator: Placebo||
The trial is a single-centre, double-blind, randomized, placebo-controlled, 2-way crossover drug interaction study with at least a 21-day washout period.
Each subject will participate in two sessions in which they will be randomized to receive either 200 mg of avanafil or matching placebo for 9 days. On Day 3 of each period, subjects will receive a single dose of warfarin (25 mg). Following the warfarin dose, pharmacokinetic and pharmacodynamic sampling will be taken over a period of 7 days. Subjects will be discharged on Day 10 following the end-of-period evaluation. There will be a washout of at least 21 days between the warfarin doses. The study medications will be administered with 240 mL of water following an overnight fast of at least 10 hours.
Blood samples (3 mL) for the assessment of R- and S-warfarin concentrations in plasma will be drawn on Day 3 prior to warfarin administration and 0.5, 1, 1.5, 2, 4, 6, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours after the warfarin administration.
Blood samples (3 mL) for the assessment of avanafil and/or metabolite concentrations will be drawn on Day 3 prior to avanafil (or placebo) administration and at 0.5, 1, and 2 hours post-dose.
Blood samples (4.5 mL) for the assessment of prothrombin time (PT) and international normalized ratio (INR) will be drawn at screening, check-in, on Day 3 prior to warfarin administration and at 6, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose.
Blood samples (4.5 mL) for collagen-induced platelet aggregation will be drawn on Day 3 prior to warfarin administration and at 1, 4, 6, 12, and 24 hours post-dose.
A blood sample (8.5 mL) for VKORC1 and CYP2C9 genotyping will be drawn at the check-in for Period 1.
The overall blood volume required for this study (assuming direct venipuncture for each sample) will be approximately 446 mL.
All subjects will be confined at the Clinical Research Unit starting in on Day -2 for diet equilibration and will remain confined for approximately 24 hours following the last study drug administration on Day 9.
Adverse events, laboratory evaluations, electrocardiogram, physical examination, and vital signs will be assessed at various times during the study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01095588
|Study Director:||Shiyin Yee, PhD||VIVUS, Inc.|